Atherosclerosis in Chemotherapy-related Cardiotoxicity

Atherosclerosis Clinical Trial

— ANTEC  

Official title:

Prognostic Significance of the Atherosclerosis in the Coronary Arteries Assessed in Computed Tomography on the Cardiotoxicity Development After Oncological Treatment

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05118178
• Other study ID #: 80/2021
• Status: Active, not recruiting
• Start date: November 15, 2021
• Est. completion date: August 15, 2024

Study information

• Verified date: February 2024
• Source: Maria Sklodowska-Curie National Research Institute of Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Cardiological complications of oncological treatment, including the most serious of them cardiotoxicity and heart failure, constitute a significant and still unsolved clinical problem. A history of hypercholesterolaemia and coronary artery disease in cancer patients, is one of the risk factors for cardiotoxicity. In recent years, a protective effect of statin treatment on the development of heart failure in cancer patients has been observed. ANTEC (Atherosclerosis iN chemoTherapy-rElated Cardiotoxicity) is a prospective observational study aimed at assessing the impact of the advancement of atherosclerotic lesions in the coronary arteries assessed in computed tomography on the development of left ventricular systolic dysfunction in cancer patients at high risk of myocardial damage. A group of 80 patients diagnosed with cancer before starting high-dose anthracycline chemotherapy (doxorubicin ≥ 240 mg / m2 or epirubicin ≥ 600 mg / m2 body weight), without a history of heart failure and coronary artery disease, will be included in the study. The total follow-up of patients was planned for 12 months. The primary endpoint is time to onset of left ventricular systolic dysfunction as assessed by echocardiography. The secondary composite endpoints include all-cause death, cardiovascular death, myocardial infarction, and stroke. Additionally, the assessment will include: the severity of atherosclerotic changes in the coronary arteries and the calcification index in computed tomography, the percentage decrease in left ventricular ejection fraction, GLS (global longitudinal strain) in echocardiography, and changes in the concentration of biomarkers involved in inflammatory and atherosclerotic processes. This is the first study of this type, which we hope will contribute to a better understanding of the pathophysiology of cardiotoxicity development and to changing the standards of management of oncological patients and improving survival in this group of patients.

Description:

Cardiological complications of oncological treatment, including the most serious:

cardiotoxicity and heart failure, remains the most dangerous cardiological complication of oncological treatment and are still unsolved clinical problem. The fear of the toxic effects of anti-cancer drugs may lead to the modification or abandonment of oncological treatment, and consequently shorten the survival time of cancer patients.

A history of hypercholesterolaemia and coronary artery disease in cancer patients, is one of the risk factors for cardiotoxicity. In recent years, a protective effect of statin treatment on the development of heart failure in cancer patients has been observed. ANTEC (Atherosclerosis iN chemoTherapy-rElated Cardiotoxicity) is a prospective observational study aimed at assessing the impact of the advancement of atherosclerotic lesions in the coronary arteries assessed in computed tomography on the development of left ventricular systolic dysfunction in cancer patients at high risk of myocardial damage. A group of 80 patients diagnosed with cancer before starting high-dose anthracycline chemotherapy (doxorubicin ≥ 240 mg / m2 or epirubicin ≥ 600 mg / m2 body weight), without a history of heart failure and coronary artery disease, will be included in the study. The total follow-up of patients was planned for 12 months. The primary endpoint is time to onset of left ventricular systolic dysfunction as assessed by echocardiography. The secondary composite endpoints include all-cause death, cardiovascular death, myocardial infarction, and stroke. Additionally, the assessment will include: the severity of atherosclerotic changes in the coronary arteries and the calcification index in computed tomography, the percentage decrease in left ventricular ejection fraction, GLS (global longitudinal strain) in echocardiography, and changes in the concentration of biomarkers involved in inflammatory and atherosclerotic processes. This is the first study of this type, which we hope will contribute to a better understanding of the pathophysiology of cardiotoxicity development and to changing the standards of management of oncological patients and improving survival in this group of patients.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: August 15, 2024
• Est. primary completion date: May 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

1. Eastern Cooperative Oncology Group (ECOG) performance status from 0 to 2.

2. Age =18 years at the time of signing the informed consent.

3. Known neoplastic disease prior to the initiation of chemotherapy with a high dose of anthracyclines (doxorubicin = 240 mg / m2 b.w. or epirubicin = 600 mg / m2 b.w.)

4. No history of heart failure (left ventricular ejection fraction = 50% as assessed by echocardiography).

5. No history of: coronary artery disease, stroke and lower limb atherosclerosis

6. At least moderate baseline cardiovascular toxicity risk according to Heart Failure Association-International Cardio-Oncology Society stratification

Exclusion Criteria:

1. History of heart failure

2. Left ventricle systolic dysfunction with LVEF <50%

3. Significant valve defect

4. Previous chemotherapy or radiation to the chest

5. Presence of any disease with a life expectancy <1 year in the opinion of the investigator.

6. Drug or alcohol abuse

7. Lack of possibility or contraindications for coronary tomography before starting chemotherapy

Related Conditions & MeSH terms

• Atherosclerosis
• Cardiotoxicity

Intervention

Diagnostic Test:
• echocardiography, computed tomography
echocardiography - including GLS and MWI computed tomography - with calcium score index

Locations

Country	Name	City	State
Poland	National Institute of Oncology	Warsaw

Sponsors (3)

Lead Sponsor	Collaborator
Maria Sklodowska-Curie National Research Institute of Oncology	Polish Cardiac Society, Servier

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The presence of atherosclerosis in the coronary arteries and the calcification index	computed tomography	from date of randomization until the end of study, up to 12 months
Other	Percentage decrease in left ventricular ejection fraction, GLS (global longitudinal strain) and MWI (myocardial work index)	echocardiography	from date of randomization until the end of study, up to 12 months
Other	Changes in the concentration of biomarkers involved in inflammatory and proatherosclerotic processes (IL-6, MPO i TNF-alfa).	blood samples	from date of randomization until the end of study, up to 12 months
Primary	Patients with left ventricular systolic dysfunction	echocardiography	from date of randomization until the end of study, up to 12 months
Secondary	Time to the secondary composite endpoint: all-cause death, cardiovascular death, myocardial infarction, and stroke	medical records	from date of randomization until the end of study, up to 12 months